Abstract Thrombosis affects 350,000 to 600,000 patients in the United States annually, and results in more than 100,000 deaths each year. Rapid and complete removal of blood clots to re-canalize blood vessels is critical. The goal of this study is to develop a high efficient endovascular method to remove blood clots by combining laser and ultrasound techniques. Cavitation is the main mechanism for both laser and ultrasound thrombolysis. Laser-based thrombolysis can easily produce vapor cavitation bubbles, but the collapse of these vapor bubbles are not as strong as the ones produced in an acoustic field because there is no driving force. Ultrasound- based thrombolysis can drive cavitation bubbles to strong collapse and generate strong local forces, but it is very difficult for ultrasound to nucleate cavitation bubbles in the blood because of lack of cavitation nuclei. The combination of laser and ultrasound can therefore overcome the limitations of both thrombolysis techniques. We propose to develop an ultrasound-facilitated endovascular laser thrombolysis technique, and test and optimize the technique in a series of in vitro and in vivo studies. The specific aims of the current study are: 1) develop a prototype device based on photo-enhanced ultrasound thrombolysis technique: in vitro study, and 2) evaluate photo-enhanced ultrasound thrombolysis in an animal model. Successful completion of this project will allow us to develop a highly efficient thrombolysis system to treat blood clot and re-canalize blood vessels in clinics. This project can potentially contribute to the many other applications including treatment and prevention of stroke, pulmonary embolism, and other vascular diseases caused by the narrowing of blood vessels.